For the selection of nine core NIH-supported projects described in this proposal, the liquid chromatography/quadrupole ion trap (LC-ion trap MS-n) mass spectroscopy system proposed would provide major enhancement. For the 14 co-investigators, key features of the proposed instrument include high combined sensitivity/scan speed in full-scan mode, multi-stage fragmentation (Ms-n), and data-dependent acquisition in automated scan mode. The projects have in common the need for identification of pharmacological agents and their in vivo metabolites, as well as their effect on cellular responses at the protein level. A major use of the instrument will be the identification and characterization of low copy number proteins and peptides in biological matrices, using methods we are developing. The specific instrument we propose is the Thermo Finnigan LCQ Deca XP ion trap MS. It would be unique in the extended geographic region of Western New York, and would be the only instrument of its kind available on a shared basis for investigators who require the direct access to the instrument and the extended use time necessary to develop new analytical approaches for protein and peptide analysis. It will be integrated into the existing Pharmaceutical Sciences mass spectrometry facility, consisting of two triple quadrupole LC/MS-MS instruments. This facility provides instrument access to a diverse population of researchers engaged in basic, applied, and clinical biomedical research, as well as analytical mass spectrometry. The facility is highly utilized, providing investigators with 4,000 hours of data acquisition on the existing LC/triple quad instruments in the last calendar year. Mass spectrometric analysis is a mainstay of many NIH-supported projects, but this region and university lacks the complementary capabilities that the Deca XP ion trap instrument will provide. Proteomics and protein chemical analysis projects are hindered by the lack of an instrument well suited for identification and characterization of proteins and peptides. Furthermore, no facility exists to provide the extended access necessary to support the development of new methods for quantitation of low-copy cellular protein transcripts or therapeutically important protein drugs. The proposed instrumentation would also enable more facile identification and characterization of small-molecule drugs and their metabolites. Given the involvement of our investigators in studies of high clinical relevance, the proposed instrument would have direct, major impact on the development of new therapies for life-threatening diseases.